Research Article Details

Article ID: A23019
PMID: 24114819
Source: Ann Hepatol
Title: Pioglitazone upregulates hepatic angiotensin converting enzyme 2 expression in rats with steatohepatitis.
Abstract: OBJECTIVE: Angiotensin II, one component of renin-angiotensin system (RAS), is formed from Ang I by the catalysing of angiotensin converting enzyme (ACE). Angiotensin II plays an important role in the development of insulin resistance. ACE2, a homologue of ACE, couterregulate the actions of angiotensin II by facilitating its breakdown to angiotensin-(1-7). RAS has been implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH). Earlier demonstration that thiazolidinediones (TZDs) improve steatohepatitis promoted us to evaluate the change of hepatic ACE2 expression in rats with high fat diet (HFD)-induced NASH and the effects of TZDs on the hepatic ACE2 expression. MATERIAL AND METHODS: Rats were divided into normal control group, high fat diet (HFD) group, and pioglitazone group. After 24 weeks of treatment with pioglitazone, a TZD, we evaluated changes in liver histology, insulin sensitivity, lipid metabolism, circulating RAS levels and hepatic ACE2 expression. RESULTS: Compared with normal controls, the concentrations of serum lipid, aminotransaminase, glucose, insulin, ACE, angiotensin II, ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression were significantly higher in rats with HFD-induced NASH. Pioglitazone significantly reduced the concentrations of serum lipid, aminotransaminase, glucose, insulin, ACE, angiotensin II while markedly raised the concentrations of serum ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression. CONCLUSION: Hepatic ACE2 expression markedly increased in rats with HFD-induced NASH and was further upregulated by pioglitazone. Hepatic ACE2 may be a new target of pioglitazone treatment for NASH.
DOI:

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details
S02 Enhance lipid metabolism triglyceride-lowering; lipid tolerance; lipid metabolism 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D366 Thiazolidinediones Chemical drug DB11898 -- -- Under clinical trials Details
D275 Pioglitazone Chemical drug DB01132 PPARG agonist Improve insulin resistance Advanced in clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details